The efficient synthesis of oligopeptides represents a contemporary challenge which has led to the development of several novel synthetic approaches. Since Merrifield introduced the use of polystyrene supports for the synthesis of oligopeptides, insoluble supports have become an indispensable tool in solid phase synthesis, especially in the synthesis of biopolymers such as polypeptides of variable length.1,2 A notable advantage of solid phase synthesis is the relative simple purification cycle, comprising the removal of excess reagents and soluble side products by simple filtration. The target product remains anchored to the solid support. The product is readily removed from the solid support and isolated by filtration. The entire process is amenable to automation. Although widely practiced in the art, solid phase synthesis retains some of the drawbacks that are typically associated with heterogeneous reaction conditions such as non-linear reaction kinetics, unequal distribution of and/or access to the reaction sites, solvation problems, and inefficient coupling rates which often necessitate a large excess of reagents to drive the reactions to completion. Further drawbacks include the low loading capacity and high cost of the solid supports, making large scale synthesis of oligopeptides using such supports very expensive. Moreover, characterization of the support-bound growing oligopeptide intermediates by common analytical methods such as TLC, NMR and MS is not practical.
The need for alternative methodologies, with the aim of restoring homogeneous reaction conditions and overcoming some of the inherent disadvantages of solid phase synthesis, has led to the development of soluble polymer supports. In recent years, the use of soluble polymer supports has received considerable attention because such “liquid phase” synthesis retains the advantages of conventional solution chemistry, while still retaining the advantage of facilitated product purification. Soluble polyethylene glycol (PEG), polyvinyl alcohol and other polymers have all been successfully employed for the synthesis of oligopeptides.3 Moreover, soluble polyethylene glycol (PEG) polymers have also been used as supports for small molecule synthesis.4 However, the use of soluble polymer supports is still limited by low loading capacity, diminished solubility during the synthesis of longer peptides, low aqueous solubility, lack of solubility in ether solvents in addition to energy intensive cooling required for purification.
More recently, a new solution-phase synthesis method based on fluorinated (fluorous) soluble supports has been advocated.5 The approach is based on the preferential solubility of the fluorous support and the fluorinated reagents in fluorous solvents (i.e. perfluoroalkanes). The non-fluorinated reagents can be readily separated from the product anchored to the fluorous support through fluorous-organic solvent partitioning6a-d or fluorous silica gel-based solid-phase extraction (SPE).6e-h However, this approach requires the use of fluorinated compounds, which are not generally readily available. Purification can be achieved through a temperature switch that causes a phase separation between the previously miscible fluorous solvent and the organic solvent, thus facilitating separation. The utility of fluorous phase methodology in organic synthesis has been demonstrated for the synthesis of oligopeptides7 and small molecules.5 The cost of perfluoroalkane solvents, the need for specialized fluorinated reagents and the energy cost associated with the temperature switch are potential limitations that limit broad application of fluorous phase organic synthesis.
Ionic liquids (ILs) have received considerable attention in recent years as environmentally benign reaction media for organic reactions.8 Because of their characteristic chemical and physical properties such as non-flammability, high thermal and chemical stability, lack of a measurable vapor pressure, high loading capacity, high ionic conductivity9 and electrochemical stability10, ionic liquids have found acceptance in diverse areas such as organic catalysis,8 electrochemical devices11 and analytical chemistry.12 Recently, ionic liquids have been used as soluble supports for catalysis,13,14 reagents and soluble supports15 supplementing the solid phase synthesis1 or other solution-phase methodologies such as soluble-polymer supported synthesis4 or fluorous phase synthesis.5 Some enzymatic reactions, have also been carried out in ionic liquids.16 Room temperature ionic liquids have also been widely explored as media for electrochemical technologies,17 chemical extractions18, and other industrial processes.19 
Most ionic liquids comprise organic cations and inorganic anions. Non-limiting examples of ionic liquids include alkylimidazolium and pyridinium salts of halides, tetrafluoroborate and hexafluorophosphate. In most cases, ionic liquids can be readily recycled. By modifying the structure of the cation and/or the anion, the solubility of ionic liquids can be tuned so that they can phase separate from organic as well as aqueous media, thus facilitating separation and purification. Ionic liquids can thus serve as viable soluble functional supports in organic synthesis. The substrate solubility can also be tuned.20 Recent reports have successfully demonstrated the utility of IL-supported synthesis (ILSS) of small molecules,21,22,23 small peptides,24 oligosaccharides25 and oligonucleotides.26 Ionic liquids have also been used as ion sources to make electronic materials,27,28 fuel cells,29 lithium batteries,30 photoelectrochemical materials,31 solar cells,32 piezoelectric sensing materials for gas sensors33, for the preparation of ionic liquid-cellulose composites,34 supported ionic membranes,35 nanoparticle stabilizing ligands,36 CO2 absorbents,37 as well as analytical materials for chromatography 38,39, mass spectrometry,40 and ion exchange absorbents.41 
IL-supported synthesis possesses most of the advantages common to solution-phase syntheses because the reactions are conducted in a substantially homogenous phase. Since the IL-bound molecules are usually highly soluble in polar organic solvents (solvents in which the reactions are conducted), but generally insoluble in less polar or non-polar solvents such as ethyl acetate, ethers and alkanes, the IL-bound species can be readily phase-separated by the addition of the less polar solvent into the polar reaction medium. However, such phase separation is not as convenient as with solid phase synthesis where simple filtration is used to isolate the solid-bound species. Moreover, the IL-bound species usually phase-separates from the solution phase as a viscous liquid, making further purification difficult. A further problem commonly observed with IL-supported synthesis is that the phase tag role played by the IL moiety is reduced when large oligomers are bound to the ionic liquid support. As is commonly observed with most soluble phase tags, the binding of large oligomers adversely affects the characteristic properties (e.g. solubility) of the ionic liquid.
The present specification refers to a number of documents, the contents of which are herein incorporated by reference in their entirety.